ABSTRACT
High-cholesterol alimentation is associated with an induction of angiotensin-converting enzyme and angiotensin II receptor expression within the vascular wall of the aorta. Despite an enhanced pressure response to angiotensin II in atherosclerotic conscious rabbits, angiotensin II-induced contraction was reduced in isolated vascular rings from the aorta and unchanged in those from the iliac artery. We, therefore, investigated whether cholesterol-induced atherosclerosis enhances overall vascular responsiveness to angiotensin II in intact animals and whether an altered arterial baroreflex sensitivity can explain the discrepancy between experiments in intact animals and isolated blood vessels. Rabbits were maintained on a high-cholesterol diet (2 g/d cholesterol plus 20 mL/d sunflower seed oil, n=11) or on a standard diet (n=12) for 12 weeks. Total serum lipids markedly increased (P<0.05). Tissue examinations 6 weeks after termination of the high-cholesterol diet revealed distinct atherosclerosis and elevated cholesterol content in the aorta (P<0.05). A high-cholesterol diet did not change baseline hemodynamic parameters. However, angiotensin II-induced increases in total peripheral resistance were larger in the atherosclerotic animals (86.3+/-13.0 versus 41.9+/-9.7 mm Hg. L(-1). min, P<0.05). In addition, the blood pressure pulse interval relationship was markedly reduced (slope: 0.80+/-0.14 versus 0. 49+/-0.06 ms/mm Hg, P<0.05), which suggested that the baroreflex blunted the angiotensin II response to a lesser extent in atherosclerotic animals. In conclusion, the overall vascular responsiveness to angiotensin II is increased in the atherosclerotic rabbit as indicated by the larger increase in total peripheral resistance. An attenuation of the arterial baroreflex sensitivity may contribute to this effect.
Subject(s)
Angiotensin II/pharmacology , Arteriosclerosis/physiopathology , Hemodynamics/drug effects , Animals , Arteriosclerosis/chemically induced , Baroreflex/physiology , Blood Pressure/drug effects , Cholesterol/metabolism , Cholesterol, Dietary/administration & dosage , Diastole , Female , Heart Rate/drug effects , Lipids/blood , Male , Rabbits , Systole , Tissue DistributionSubject(s)
Blood Pressure Monitors , Blood Volume/physiology , Fingers/blood supply , Plethysmography, Impedance/instrumentation , Pulse , Signal Processing, Computer-Assisted/instrumentation , Humans , Models, Cardiovascular , Regional Blood Flow/physiology , Software , Vascular Resistance/physiologyABSTRACT
A method for instantaneous measurements and representations of myocardial pressure-velocity relations permitting the analysis of various contractility parameters is described. Basing on a modified two-element model of cardiac muscle the measurement of the relative shortening velocity vce = dp/dt(p) of the contractile elements is carried out by a special analog computer, which calculates the quotient (dp/dt) to the simultaneous left ventricular pressure p. Electronic differentiation of the logarithm of pressure-proportional input voltages is used. The p-v-diagram can be displayed on x-y-oscilloscopes. Over an input voltage range of 20 mV---20V the quotient can be measured within the range of 20 sec-1---250 sec-1. Output voltages can be calibrated automatically. Between (dp/dt)p-1 determined by conventional methods and the dlnp/dt calcuated electronically there exists a correlation gamma = 0.995. An additional electronic circuit which permits the determination of a contractility parameter indicates the point of (dp/dt)max on the p-v-relation display. The application of the method in experimental studies under inotropic changes in the rabbit heart in situ following beta-receptor blockade is demonstrated.
